Afadin: A Key Molecule Essential for Structural Organization of Cell–Cell Junctions of Polarized Epithelia during Embryogenesis

doi:10.1083/jcb.146.5.1117

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© The Rockefeller University Press, 0021-9525/1999/9/1117/ $5.00
The Journal of Cell Biology, Volume 146, Number 5, September 6, 1999 1117-1132

Afadin: A Key Molecule Essential for Structural Organization of Cell–Cell Junctions of Polarized Epithelia during Embryogenesis

Wataru Ikeda^a, Hiroyuki Nakanishi^b, Jun Miyoshi^b, Kenji Mandai^b, Hiroyoshi Ishizaki^b, Miki Tanaka^b, Atushi Togawa^b, Kenichi Takahashi^b, Hideo Nishioka^b, Hisahiro Yoshida^c, Akira Mizoguchi^d, Shin-ichi Nishikawa^c, and Yoshimi Takai^a,b
^a Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Osaka 565-0871, Japan
^b Takai Biotimer Project, Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, JCR Pharmaceuticals Co., Ltd., Kobe 651-2241, Japan
^c Department of Molecular Genetics, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan
^d Department of Anatomy and Neurobiology, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan

Correspondence to: Yoshimi Takai, Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. Tel:81-6-6879-3410 Fax:81-6-6879-3419 E-mail:ytakai{at}molbio.med.osaka-u.ac.jp.

Afadin is an actin filament–binding protein that bindsto nectin, an immunoglobulin-like cell adhesion molecule, andis colocalized with nectin at cadherin-based cell–celladherens junctions (AJs). To explore the function of afadinin cell–cell adhesion during embryogenesis, we generatedafadin^-/- mice and embryonic stem cells. In wild-type mice atembryonic days 6.5–8.5, afadin was highly expressed inthe embryonic ectoderm and the mesoderm, but hardly detectedin the extraembryonic regions such as the visceral endoderm.Afadin^-/- mice showed developmental defects at stages duringand after gastrulation, including disorganization of the ectoderm,impaired migration of the mesoderm, and loss of somites andother structures derived from both the ectoderm and the mesoderm.Cystic embryoid bodies derived from afadin^-/- embryonic stemcells showed normal organization of the endoderm but disorganizationof the ectoderm. Cell–cell AJs and tight junctions wereimproperly organized in the ectoderm of afadin^-/- mice and embryoidbodies. These results indicate that afadin is highly expressedin the ectoderm- derived cells during embryogenesis and playsa key role in proper organization of AJs and tight junctionsof the highly expressing cells, which is essential for propertissue morphogenesis.

Key Words: afadin, cadherin, ZO-1, cell–cell junctions, embryogenesis

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